Trial Outcomes & Findings for A Study to Determine the Effect of Nitroglycerin Ointment 0.4% (Cellegesic) on the Pain Associated With Chronic Anal Fissures (NCT NCT00522041)

NCT ID: NCT00522041

Last Updated: 2016-11-03

Results Overview

Participants rated the pain associated with their chronic anal fissure over the preceding 24 hours on a 100 mm visual analog scale at Baseline and on Days 14 through 18. The average pain rating on Days 14 through 18 was calculated and used to determine the change from Baseline. The left-end of the visual analog scale was labelled "least possible pain" and the right-end of the visual analog scale was labelled "worst possible pain". The pain rating ranged from 0 to 100, with a higher score indicating more pain. A negative change score indicated improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

248 participants

Primary outcome timeframe

Baseline to Day 18

Results posted on

2016-11-03

Participant Flow

Participant milestones

Participant milestones
Measure	Cellegesic (Nitroglycerin 0.4%) Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Overall Study STARTED	123	125
Overall Study Received Treatment	123	124
Overall Study COMPLETED	106	113
Overall Study NOT COMPLETED	17	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Cellegesic (Nitroglycerin 0.4%) Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Overall Study Adverse Event	9	3
Overall Study Protocol Violation	2	0
Overall Study Lost to Follow-up	1	4
Overall Study Voluntary withdrawal	5	4
Overall Study Did not receive treatment	0	1

Baseline Characteristics

A Study to Determine the Effect of Nitroglycerin Ointment 0.4% (Cellegesic) on the Pain Associated With Chronic Anal Fissures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cellegesic (Nitroglycerin 0.4%) n=123 Participants Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo n=124 Participants Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Total n=247 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	114 Participants n=5 Participants	117 Participants n=7 Participants	231 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Age, Continuous	46.5 years STANDARD_DEVIATION 12.61 • n=5 Participants	43.4 years STANDARD_DEVIATION 13.22 • n=7 Participants	45.0 years STANDARD_DEVIATION 12.99 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	58 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	66 Participants n=7 Participants	131 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	31 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=5 Participants	93 Participants n=7 Participants	193 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	21 Participants n=5 Participants	16 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) White	99 Participants n=5 Participants	96 Participants n=7 Participants	195 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 18

Population: Intent-to-treat population: All randomized participants who had applied the study medication at least once.

Outcome measures

Outcome measures
Measure	Cellegesic (Nitroglycerin 0.4%) n=123 Participants Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo n=124 Participants Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Change From Baseline in Pain Intensity at Days 14-18	-40.4 Units on a scale Standard Error 3.12	-34.9 Units on a scale Standard Error 3.04

SECONDARY outcome

Timeframe: Baseline to Day 21

Population: Intent-to-treat population: All randomized participants who had applied the study medication at least once. Only participants with an improvement in pain intensity were included in the analysis.

Participants rated the pain associated with their chronic anal fissure over the preceding 24 hours on a 100 mm visual analog scale (VAS) at Baseline and on each of the 21 treatment days of the study. The left-end of the visual analog scale was labelled "least possible pain" and the right-end of the visual analog scale was labelled "worst possible pain". The pain rating ranged from 0 to 100, with a higher score indicating more pain. Improvement was defined as either a ≥ 50% decrease or a ≥ 10 mm decrease from Baseline in rated pain intensity.

Outcome measures

Outcome measures
Measure	Cellegesic (Nitroglycerin 0.4%) n=123 Participants Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo n=124 Participants Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Time to an Improvement in Pain Intensity ≥ 50% decrease	10.7 Days Standard Error 0.6	13.2 Days Standard Error 0.7
Time to an Improvement in Pain Intensity ≥ 10 mm decrease	6.1 Days Standard Error 0.5	7.2 Days Standard Error 0.6

SECONDARY outcome

Timeframe: Baseline to Day 18

Population: Intent-to-treat population: All randomized participants who had applied the study medication at least once.

Participants rated the pain associated with their chronic anal fissure over the preceding 24 hours on a 100 mm visual analog scale at Baseline and on Days 14 through 18. The average pain rating on Days 14 through 18 was calculated. The left-end of the visual analog scale was labelled "least possible pain" and the right-end of the visual analog scale was labelled "worst possible pain". The pain rating ranged from 0 to 100, with a higher score indicating more pain. A responder was defined as a participant with either a ≥ 50% decrease or a ≥ 10 mm decrease from Baseline in the 24 hour average pain intensity averaged over Days 14 to 18.

Outcome measures

Outcome measures
Measure	Cellegesic (Nitroglycerin 0.4%) n=123 Participants Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo n=124 Participants Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Percentage of Responders ≥ 50% decrease	72.4 Percentage of responders	64.5 Percentage of responders
Percentage of Responders ≥ 10 mm decrease	88.6 Percentage of responders	85.5 Percentage of responders

Adverse Events

Cellegesic (Nitroglycerin 0.4%)

Serious events: 2 serious events

Other events: 96 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cellegesic (Nitroglycerin 0.4%) n=123 participants at risk Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo n=124 participants at risk Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/123 Safety population: All participants who received at least 1 application of study medication.	0.81% 1/124 Safety population: All participants who received at least 1 application of study medication.
Infections and infestations Osteomyelitis	0.81% 1/123 Safety population: All participants who received at least 1 application of study medication.	0.00% 0/124 Safety population: All participants who received at least 1 application of study medication.
Surgical and medical procedures Anal sphincterotomy	0.81% 1/123 Safety population: All participants who received at least 1 application of study medication.	0.00% 0/124 Safety population: All participants who received at least 1 application of study medication.

Other adverse events

Other adverse events
Measure	Cellegesic (Nitroglycerin 0.4%) n=123 participants at risk Participants applied Cellegesic 375 mg ointment containing approximately 1.5 mg of nitroglycerin anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.	Placebo n=124 participants at risk Participants applied placebo 375 mg ointment anally twice daily for 21 days. In addition, participants took acetaminophen 650 mg orally twice daily for 21 days.
Nervous system disorders Headache	69.9% 86/123 Safety population: All participants who received at least 1 application of study medication.	47.6% 59/124 Safety population: All participants who received at least 1 application of study medication.
Nervous system disorders Dizziness	4.9% 6/123 Safety population: All participants who received at least 1 application of study medication.	1.6% 2/124 Safety population: All participants who received at least 1 application of study medication.
Gastrointestinal disorders Nausea	1.6% 2/123 Safety population: All participants who received at least 1 application of study medication.	4.0% 5/124 Safety population: All participants who received at least 1 application of study medication.
Gastrointestinal disorders Diarrhoea	3.3% 4/123 Safety population: All participants who received at least 1 application of study medication.	3.2% 4/124 Safety population: All participants who received at least 1 application of study medication.
Infections and infestations Sinusitis	2.4% 3/123 Safety population: All participants who received at least 1 application of study medication.	0.81% 1/124 Safety population: All participants who received at least 1 application of study medication.

Additional Information

Susan Fox, PhD

Allergan plc

Phone: 201-427-8225

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication statement in clinical trial agreement.
Publication restrictions are in place

Restriction type: OTHER